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Nuclear translocation of PKC-alpha is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs)

Author(s)
Poli, AlessandroRatti, StefanoFinelli, CarloMongiorgi, SaraClissa, CristinaLonetti, AnnalisaCappellini, AlessandraCatozzi, AlessiaBarraco, MarilenaSuh, Pann-GhillManzoli, LuciaMcCubrey, James A.Cocco, LucioFollo, Matilde Y.
Issued Date
2018-02
DOI
10.1096/fj.201700690R
URI
https://scholarworks.unist.ac.kr/handle/201301/25528
Fulltext
http://www.fasebj.org/doi/10.1096/fj.201700690R
Citation
FASEB JOURNAL, v.32, no.2, pp.681 - 692
Abstract
PI-PLC beta 1 is involved in cell proliferation, differentiation, and myelodysplastic syndrome (MDS) pathogenesis. Moreover, the increased activity of PI-PLC beta 1 reduces the expression of PKC-alpha, which, in turn, delays the cell proliferation and is linked to erythropoiesis. Lenalidomide is currently used in low-risk patients with MDS and del(5q), where it can suppress the del(5q) clone and restore normal erythropoiesis. In this study, we analyzed the effect of lenalidomide on 16 patients with low-risk del(5q) MDS, as well as del(5q) and non-del(5q) hematopoietic cell lines, mainly focusing on erythropoiesis, cell cycle, and PI-PLC beta 1/PKC-alpha signaling. Overall, 11 patients were evaluated clinically, and 10 (90%) had favorable responses; the remaining case had a stable disease. At a molecular level, both responder patients and del(5q) cells showed a specific induction of erythropoiesis, with a reduced gamma/beta-globin ratio, an increase in glycophorin A, and a nuclear translocation of PKC-alpha. Moreover, lenalidomide could induce a selective G(0)/G(1) arrest of the cell cycle in del(5q) cells, slowing down the rate proliferation in those cells. Altogether, our results could not only better explain the role of PI-PLC beta 1/PKC-alpha signaling in erythropoiesis but also lead to a better comprehension of the lenalidomide effect on del(5q) MDS and pave the way to innovative, targeted therapies.
Publisher
FEDERATION AMER SOC EXP BIOL
ISSN
0892-6638
Keyword (Author)
nucleuserythropoiesislenalidomidechromosome 5q deletion
Keyword
ACUTE LYMPHOBLASTIC-LEUKEMIAPHOSPHOLIPASE-CRISK MDSSIGNALING PATHWAYSK562 CELLSLENALIDOMIDEPI-PLC-BETA-1AZACITIDINEINVOLVEMENTACTIVATION

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